The gut-associated immune system maintains the normal equilibrium with intestinal antigens. The objectives of this proposal are to determine the role played by intestinal epithelium in modulating the absorption of antigen from the gut lumen, and to determine the conditions which lead to the dispersal of antibody-producing cells along the gastrointestinal tract after absorption of an antigen. In particular, the role of the epithelium and lymphcytes of Peyer's patches, appendix, and bursa of Fabricius in antigen absorption and production of plasma cells will be explored. Horseradish peroxidase and ferritin will be used as traceable, quantifiable antigen which will be introduced into the gut lumen of animals previously immunized to one of those antigens. The gut epithelium will be isolated and the quantity of antigen absorbed will be compared with that absorbed by untreated animals or animals immunized with a different antigen. The quantity of antigen adsorbed to the surface of the epithelium will be compared with the quantity actually taken into the cell. The effect of immunization on adsorption, particularly in the surface enteric coating, will be determined. In addition, the localization of antigen, both associated with epithelium and with lamina propria, will be carried out by light and electron microscopy. Absorption studies will be correlated with the level of circulating antibody. The effect of passive transfer of antibodies and cells will be determined. Migration and differentiation of B cells will be followed by first giving a "priming" intraperitoneal injection of horseradish peroxidase or immunoglobulin. The same antigen will subsequently be introduced into the small intestine, appendix, or bursa of Fabricius. Next, antibody-containing plasma cells will be sought in different levels of the gut, using cytochemical and fluorescence techniques. The pattern and degree of migration and differentiation may then be used to determine the conditions necessary to cause this response.